One of the characteristics of a disease state is the imbalance of chemicals that may develop as compared to the normal, healthy levels of the materials. For example, many abnormal conditions such as infection, inflammation and trauma are characterized by an elevation in C-reactive protein plasma levels and a decrease in fibronectin (Fn) plasma levels. C-reactive protein (CRP) is a member of the pentraxin family of proteins and is formed of five identical subunits that are noncovalently linked to one another. It is one of the many acute-phase proteins, increasing by roughly 1,000-fold in response to the onset of trauma. Fn, on the other hand, is a negative acute phase reactant, and levels of the soluble form of the protein as is found in plasma as well as other bodily fluids decrease rapidly following tissue damage or destruction. Fn is formed of a single polypeptide chain that includes three different types of repeating modules and is involved in many cellular processes including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion.
Another characteristic of an abnormal physical condition is an alteration in how the chemicals of the body interact with one another. For example, at normal physiological condition CRP and Fn do not interact. It has been discovered, however, that binding of Fn by CRP increases greatly at mildly acidic conditions, which is a characteristic feature of the inflammatory locus.
It is believed that if the chemical state at a site of abnormal physical condition may be altered to more closely resemble that of the normal state, healing and recovery may better proceed. For example, if the chemistry that characterizes a disease site, e.g., a chronic wound or an inflammation site, may be brought closer in line with the healthy chemistry, improvement and healing at the disease site may rapidly follow.
Accordingly, what is needed in the art are methods for the identification of compounds that may then be utilized to alter the chemistry at a site of disease or damage to more closely resemble the healthy, desired chemistry and thus promote a return to health at the site. In addition, what is needed in the art are methods and compounds for examining the chemistry of disease states, so as to improve understanding of both the disease state itself as well as the activity of active compounds upon development and recovery of the disease state.